scholarly journals Common Features in lncRNA Annotation and Classification: A Survey

2021 ◽  
Vol 7 (4) ◽  
pp. 77
Author(s):  
Christopher Klapproth ◽  
Rituparno Sen ◽  
Peter F. Stadler ◽  
Sven Findeiß ◽  
Jörg Fallmann
Keyword(s):  
Gene Expression ◽  
Disease Progression ◽  
In Silico ◽  
Therapeutic Targets ◽  
Untranslated Regions ◽  
Protein Coding ◽  
Coding Sequence ◽  
Common Features ◽  
Research Gap ◽  
Non Coding Rnas

Long non-coding RNAs (lncRNAs) are widely recognized as important regulators of gene expression. Their molecular functions range from miRNA sponging to chromatin-associated mechanisms, leading to effects in disease progression and establishing them as diagnostic and therapeutic targets. Still, only a few representatives of this diverse class of RNAs are well studied, while the vast majority is poorly described beyond the existence of their transcripts. In this review we survey common in silico approaches for lncRNA annotation. We focus on the well-established sets of features used for classification and discuss their specific advantages and weaknesses. While the available tools perform very well for the task of distinguishing coding sequence from other RNAs, we find that current methods are not well suited to distinguish lncRNAs or parts thereof from other non-protein-coding input sequences. We conclude that the distinction of lncRNAs from intronic sequences and untranslated regions of coding mRNAs remains a pressing research gap.

scholarly journals Long non-coding RNAs in brain tumors

NAR Cancer ◽  
2021 ◽  
Vol 3 (1) ◽  
Author(s):  
Keisuke Katsushima ◽  
George Jallo ◽  
Charles G Eberhart ◽  
Ranjan J Perera
Keyword(s):  
Gene Expression ◽  
Brain Tumors ◽  
Brain Cancer ◽  
Regulation Of Gene Expression ◽  
Therapeutic Targets ◽  
Diagnostic Biomarkers ◽  
Cancer Pathogenesis ◽  
Current State ◽  
Non Coding Rnas ◽  
Post Transcriptional Regulation

Abstract Long non-coding RNAs (lncRNAs) have been found to be central players in the epigenetic, transcriptional and post-transcriptional regulation of gene expression. There is an accumulation of evidence on newly discovered lncRNAs, their molecular interactions and their roles in the development and progression of human brain tumors. LncRNAs can have either tumor suppressive or oncogenic functions in different brain cancers, making them attractive therapeutic targets and biomarkers for personalized therapy and precision diagnostics. Here, we summarize the current state of knowledge of the lncRNAs that have been implicated in brain cancer pathogenesis, particularly in gliomas and medulloblastomas. We discuss their epigenetic regulation as well as the prospects of using lncRNAs as diagnostic biomarkers and therapeutic targets in patients with brain tumors.

Role of MicroRNAs and Long Non-Coding RNAs in Regulating Angiogenesis in Human Breast Cancer- A Molecular Medicine Perspective

2021 ◽  
Vol 22 ◽  
Author(s):  
Vandana Golhani ◽  
Suman Kumar Ray ◽  
Sukhes Mukherjee
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Signaling Pathways ◽  
Cancer Therapeutics ◽  
Molecular Medicine ◽  
Dependent Manner ◽  
Protein Coding ◽  
Controlled Systems ◽  
Expression Of Genes ◽  
Non Coding Rnas

: MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are proficient in regulating gene expression post-transcriptionally. Considering the recent trend in exploiting non-coding RNAs (ncRNAs) as cancer therapeutics, the potential use of miRNAs and lncRNAs as biomarkers and novel therapeutic agents against angiogenesis is an important scientific aspect. An estimated 70% of the genome is actively transcribed, only 2% of which codes for known protein-coding genes. Long noncoding RNAs (lncRNAs) are a large and diverse class of RNAs > 200 nucleotides in length, and not translated into protein, and are of utmost importance and it governs the expression of genes in a temporal, spatial, and cell context-dependent manner. Angiogenesis is an essential process for organ morphogenesis and growth during development, and it is relevant during the repair of wounded tissue in adults. It is coordinated by an equilibrium of pro-and anti-angiogenic factors; nevertheless, when affected, it promotes several diseases, including breast cancer. Signaling pathways involved here are tightly controlled systems that regulate the appropriate timing of gene expression required for the differentiation of cells down a particular lineage essential for proper tissue development. Lately, scientific reports are indicating that ncRNAs, such as miRNAs, and lncRNAs, play critical roles in angiogenesis related to breast cancer. The specific roles of various miRNAs and lncRNAs in regulating angiogenesis in breast cancer, with particular focus on the downstream targets and signaling pathways regulated by these ncRNAs with molecular medicine perspective, are highlighted in this write-up.

Protein-RNA interactome analysis reveals wide association of KSHV ORF57 with host non-coding RNAs and polysomes

2021 ◽  
Author(s):  
Beatriz Alvarado-Hernandez ◽  
Yanping Ma ◽  
Nishi R. Sharma ◽  
Vladimir Majerciak ◽  
Alexei Lobanov ◽  
...  
Keyword(s):  
Gene Expression ◽  
Rna Splicing ◽  
Rna Binding ◽  
Viral Gene Expression ◽  
Viral Gene ◽  
28S Rrna ◽  
Protein Coding ◽  
Infected Cells ◽  
Non Coding Rnas ◽  
Rna Interaction

Kaposi’s sarcoma-associated herpesvirus (KSHV) ORF57 is an RNA-binding post-transcriptional regulator. We recently applied an affinity-purified anti-ORF57 antibody to conduct ORF57-CLIP (Cross-linking Immunoprecipitation) in combination with RNA-sequencing (CLIP-seq) and analyzed the genome-wide host RNA transcripts in association with ORF57 in BCBL-1 cells with lytic KSHV infection. Mapping of the CLIPed RNA reads to the human genome (GRCh37) revealed that most of the ORF57-associated RNA reads were from rRNAs. The remaining RNA reads mapped to several classes of host non-coding and protein-coding mRNAs. We found ORF57 binds and regulates expression of a subset of host lncRNAs, including LINC00324, LINC00355, and LINC00839 which are involved in cell growth. ORF57 binds snoRNAs responsible for 18S and 28S rRNA modifications, but does not interact with fibrillarin and NOP58. We validated ORF57 interactions with 67 snoRNAs by ORF57-RNA immunoprecipitation (RIP)-snoRNA-array assays. Most of the identified ORF57 rRNA binding sites (BS) overlap with the sites binding snoRNAs. We confirmed ORF57-snoRA71B RNA interaction in BCBL-1 cells by ORF57-RIP and Northern blot analyses using a 32 P-labeled oligo probe from the 18S rRNA region complementary to snoRA71B. Using RNA oligos from the rRNA regions that ORF57 binds for oligo pulldown-Western blot assays, we selectively verified ORF57 interactions with 5.8S and 18S rRNAs. Polysome profiling revealed that ORF57 associates with both monosomes and polysomes and its association with polysomes increases PABPC1 binding to, but prevent Ago2 from polysomes. Our data indicate a functional correlation with ORF57 binding and suppression of Ago2 activities for ORF57 promotion of gene expression. Significance As an RNA-binding protein, KSHV ORF57 regulates RNA splicing, stability, and translation and inhibits host innate immunity by blocking the formation of RNA granules in virus infected cells. In this report, ORF57 was found to interact many host non-coding RNAs, including lncRNAs, snoRNAs and ribosomal RNAs to carry out additional unknown functions. ORF57 binds a group of lncRNAs via the identified RNA motifs by ORF57 CLIP-seq to regulate their expression. ORF57 associates with snoRNAs independently of fibrillarin and NOP58 proteins, and with ribosomal RNA in the regions that commonly bind snoRNAs. Knockdown of fibrillarin expression decreases the expression of snoRNAs and CDK4, but not affect viral gene expression. More importantly, we found that ORF57 binds translationally active polysomes and enhances PABPC-1 but prevents Ago2 association with polysomes. Data provide a compelling evidence on how ORF57 in KSHV infected cells might regulate protein synthesis by blocking Ago2’s hostile activities on translation.

microRNAs: a new frontier in kallikrein research

2008 ◽  
Vol 389 (6) ◽  
Author(s):  
George M. Yousef
Keyword(s):  
Gene Expression ◽  
Human Tissue ◽  
In Silico ◽  
Regulatory Mechanism ◽  
Transcriptional Level ◽  
Regulate Gene Expression ◽  
New Frontier ◽  
Experimental Approaches ◽  
Non Coding Rnas ◽  
Regulate Gene

Abstract microRNAs (miRNAs) are a recently discovered class of small non-coding RNAs that regulate gene expression. Rapidly accumulating evidence has revealed that miRNAs are associated with cancer. The human tissue kalli-krein gene family is the largest contiguous family of proteases in the human genome, containing 15 genes. Many kallikreins have been reported as potential tumor markers. In this review, recent bioinformatics and experimental evidence is presented indicating that kallikreins are potential miRNA targets. The available experimental approaches to investigate these interactions and the potential diagnostic and therapeutic applications are also discussed. miRNAs represent a possible regulatory mechanism for controlling kallikrein expression at the post-transcriptional level. Many miRNAs were predicted to target kallikreins and a single miRNA can target more than one kallikrein. Recent evidence suggests that miRNAs can also exert ‘quantitative’ control of kallikreins by utilizing multiple targeting sites in the kallikrein mRNA. More research is needed to experimentally verify the in silico predictions and to investigate the possible role in tumor initiation and/or progression.

scholarly journals Rapidly evolving protointrons in Saccharomyces genomes revealed by a hungry spliceosome

2019 ◽  
Author(s):  
Jason Talkish ◽  
Haller Igel ◽  
Rhonda J. Perriman ◽  
Lily Shiue ◽  
Sol Katzman ◽  
...  
Keyword(s):  
Gene Expression ◽  
Protein Isoforms ◽  
Yeast Genome ◽  
Protein Coding ◽  
Coding Sequences ◽  
New Genes ◽  
Eukaryotic Genes ◽  
Non Coding Rnas ◽  
The Creation ◽  
New Protein

AbstractIntrons are a prevalent feature of eukaryotic genomes, yet their origins and contributions to genome function and evolution remain mysterious. In budding yeast, repression of the highly transcribed intron-containing ribosomal protein genes (RPGs) globally increases splicing of non-RPG transcripts through reduced competition for the spliceosome. We show that under these “hungry spliceosome” conditions, splicing occurs at more than 150 previously unannotated locations we call protointrons that do not overlap known introns. Protointrons use a less constrained set of splice sites and branchpoints than standard introns, including in one case AT-AC in place of GT-AG. Protointrons are not conserved in all closely related species, suggesting that most are not under selection. Some are found in non-coding RNAs (e. g. CUTs and SUTs), where they may contribute to the creation of new genes. Others are found across boundaries between noncoding and coding sequences, or within coding sequences, where they offer pathways to the creation of new protein variants, or new regulatory controls for existing genes. We define protointrons as (1) nonconserved intron-like sequences that are (2) infrequently spliced, and importantly (3) are not currently understood to contribute to gene expression or regulation in the way that standard introns function. A very few protointrons in S. cerevisiae challenge this classification by their increased splicing frequency and potential function, consistent with the proposed evolutionary process of “intronization”, whereby new standard introns are created. This snapshot of intron evolution highlights the important role of the spliceosome in the expansion of transcribed genomic sequence space, providing a pathway for the rare events that may lead to the birth of new eukaryotic genes and the refinement of existing gene function.Author SummaryThe protein coding information in eukaryotic genes is broken by intervening sequences called introns that are removed from RNA during transcription by a large protein-RNA complex called the spliceosome. Where introns come from and how the spliceosome contributes to genome evolution are open questions. In this study, we find more than 150 new places in the yeast genome that are recognized by the spliceosome and spliced out as introns. Since they appear to have arisen very recently in evolution by sequence drift and do not appear to contribute to gene expression or its regulation, we call these protointrons. Protointrons are found in both protein-coding and non-coding RNAs and are not efficiently removed by the splicing machinery. Although most protointrons are not conserved, a few are spliced more efficiently, and are located where they might begin to play functional roles in gene expression, as predicted by the proposed process of intronization. The challenge now is to understand how spontaneously appearing splicing events like protointrons might contribute to the creation of new genes, new genetic controls, and new protein isoforms as genomes evolve.

scholarly journals Highly Divergent Neuropeptide - non-coding RNA regulatory networks underpin variant host-finding behaviours in Steinernema species infective juveniles

2020 ◽  
Author(s):  
Neil D. Warnock ◽  
Erwan Atcheson ◽  
Ciaran McCoy ◽  
Johnathan J. Dalzell
Keyword(s):  
Gene Expression ◽  
Small Rna ◽  
Regulatory Networks ◽  
Host Finding ◽  
Protein Coding ◽  
Rna Analysis ◽  
New Family ◽  
Non Coding Rna ◽  
Non Coding Rnas ◽  
Shared Gene

AbstractWe conducted a transcriptomic and small RNA analysis of infective juveniles (IJs) from three behaviourally distinct Steinernema species. Substantial variation was found in the expression of shared gene orthologues, revealing gene expression signatures that correlate with behavioural states. 97% of predicted microRNAs are novel to each species. Surprisingly, our data provide evidence that isoform variation can effectively convert protein-coding neuropeptide genes into non-coding transcripts, which may represent a new family of long non-coding RNAs. These data suggest that differences in neuropeptide gene expression, isoform variation, and small RNA interactions could contribute to behavioural differences within the Steinernema genus.

scholarly journals Functional Screening Techniques to Identify Long Non-Coding RNAs as Therapeutic Targets in Cancer

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3695
Author(s):  
Kathleen M. Lucere ◽  
Megan M. R. O’Malley ◽  
Sarah D. Diermeier
Keyword(s):  
Antisense Oligonucleotides ◽  
High Throughput Screening ◽  
Large Scale ◽  
Therapeutic Targets ◽  
Functional Screening ◽  
Protein Coding ◽  
Non Coding Rnas ◽  
New Therapeutic Targets ◽  
Functional Screens ◽  
Screening Approaches

Recent technological advancements such as CRISPR/Cas-based systems enable multiplexed, high-throughput screening for new therapeutic targets in cancer. While numerous functional screens have been performed on protein-coding genes to date, long non-coding RNAs (lncRNAs) represent an emerging class of potential oncogenes and tumor suppressors, with only a handful of large-scale screens performed thus far. Here, we review in detail currently available screening approaches to identify new lncRNA drivers of tumorigenesis and tumor progression. We discuss the various approaches of genomic and transcriptional targeting using CRISPR/Cas9, as well as methods to post-transcriptionally target lncRNAs via RNA interference (RNAi), antisense oligonucleotides (ASOs) and CRISPR/Cas13. We discuss potential advantages, caveats and future applications of each method to provide an overview and guide on investigating lncRNAs as new therapeutic targets in cancer.

scholarly journals A community-driven roadmap to advance research on translated open reading frames detected by Ribo-seq

2021 ◽  
Author(s):  
Jonathan M Mudge ◽  
Jorge Ruiz-Orera ◽  
John R Prensner ◽  
Marie A Brunet ◽  
Jose Manuel Gonzalez ◽  
...  
Keyword(s):  
Gene Annotation ◽  
Ribosome Profiling ◽  
Open Reading Frames ◽  
Untranslated Regions ◽  
Biological Databases ◽  
Protein Coding ◽  
Circular Problem ◽  
Advance Research ◽  
Non Coding Rnas ◽  
Reading Frames

Ribosome profiling (Ribo-seq) has catalyzed a paradigm shift in our understanding of the translational vocabulary of the human genome, discovering thousands of translated open reading frames (ORFs) within long non-coding RNAs and presumed untranslated regions of protein-coding genes. However, reference gene annotation projects have been circumspect in their incorporation of these ORFs due to uncertainties about their experimental reproducibility and physiological roles. Yet, it is indisputable that certain Ribo-seq ORFs make stable proteins, others mediate gene regulation, and many have medical implications. Ultimately, the absence of standardized ORF annotation has created a circular problem: while Ribo-seq ORFs remain unannotated by reference biological databases, this lack of characterisation will thwart research efforts examining their roles. Here, we outline the initial stages of a community-led effort supported by GENCODE / Ensembl, HGNC and UniProt to produce a consolidated catalog of human Ribo-seq ORFs.

scholarly journals Functional and transcriptional profiling of non-coding RNAs in yeast reveal context-dependent phenotypes and widespread in trans effects on the protein regulatory network

2020 ◽  
Author(s):  
Laura Natalia Balarezo-Cisneros ◽  
Steven Parker ◽  
Marcin G Fraczek ◽  
Soukaina Timouma ◽  
Ping Wang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Environmental Conditions ◽  
Mode Of Action ◽  
Protein Coding ◽  
Protein Coding Genes ◽  
Genome Wide ◽  
In Trans ◽  
Non Coding Rnas ◽  
The Impact

AbstractNon-coding RNAs (ncRNAs), including the more recently identified Stable Unannotated Transcripts (SUTs) and Cryptic Unstable Transcripts (CUTs), are increasingly being shown to play pivotal roles in the transcriptional and post-transcriptional regulation of genes in eukaryotes. Here, we carried out a large-scale screening of ncRNAs in Saccharomyces cerevisiae, and provide evidence for SUT and CUT function. Phenotypic data on 372 ncRNA deletion strains in 23 different growth conditions were collected, identifying ncRNAs responsible for significant cellular fitness changes. Transcriptome profiles were assembled for 18 haploid ncRNA deletion mutants and 2 essential ncRNA heterozygous deletants. Guided by the resulting RNA-seq data we analysed the genome-wide dysregulation of protein coding genes and non-coding transcripts. Novel functional ncRNAs, SUT125, SUT126, SUT035 and SUT532 that act in trans by modulating transcription factors were identified. Furthermore, we described the impact of SUTs and CUTs in modulating coding gene expression in response of different environmental conditions, regulating important biological process such as respiration (SUT125, SUT126, SUT035, SUT432), steroid biosynthesis (CUT494, SUT530, SUT468) or rRNA processing (SUT075 and snR30). Overall, this data captures and integrates the regulatory and phenotypic network of ncRNAs and protein coding genes, providing genome-wide evidence of the impact of ncRNAs on cellular homeostasis.Author SummaryThe yeast genome contains 25% of non-coding RNA molecules (ncRNAs), which do not translate into proteins but are involved in regulation of gene expression. ncRNAs can affect nearby genes by physically interfering with their transcription (cis mode of action), or they interact with DNA, proteins or others RNAs to regulate the expression of distant genes (trans mode of action). Examples of cis-acting ncRNAs have been broadly described, however genome-wide studies to identify functional trans-acting ncRNAs involved in global gene regulation are still lacking. Here, we used the ncRNA yeast deletion collection to score their impact on cellular function in different environmental conditions. A group of 20 ncRNAs mutants with broad fitness diversity were selected to investigate their effect on the protein and ncRNA expression network. We showed a high correlation between altered phenotypes and global transcriptional changes, in an environmental dependent manner. We confirmed the widespread trans acting expressional regulation of ncRNAs in the genome and their role in affecting transcription factors. These findings support the notion of the involvement on ncRNAs in fine tuning the cellular expression via regulations of TFs, as an advantageous RNA-mediated mechanism that can be fast and cost-effective for the cells.

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